Signal transduction mechanism by which lipopolysaccharides from various periodontopathic bacteria induce murine B lymphocyte activation

本研究利用牙龈卟啉菌（Porphyronwnas gingivalis）以及其他牙周病细菌，包括中间普雷沃菌（Prevotella intermedia）、放线菌(Actinobacillus放线菌comitans放线菌(Actinobacillus放线菌comitans放线菌（Actinobacillus放线菌comitans）和腐蚀艾肯菌（eikenelleserodens）（分别为PgLPS、AaLPS、PiLPS和EiLPS）的脂多糖（LPS），研究了脂多糖介导淋巴细胞后期细胞反应的信号转导机制的性质。用单克隆抗磷酸酪氨酸抗体进行Western blot检测，所有LPS和大肠杆菌LPS （EcLPS）均诱导C3H/HeN小鼠B淋巴细胞酪氨酸磷酸化。而在lps低应答的C3H/HeJ B淋巴细胞中，PgLPS和PiLPS可以诱导触发信号，而AaLPS和EiLPS则不能。此外，来自明尼苏达沙门氏菌的脂质A也能诱导C3H/HeN B淋巴细胞酪氨酸磷酸化。据报道，PgLPS和PiLPS的脂质A部分与EcLPS、AaLPS和EiLPS有很大的不同。这些结果让我们更有信心。提示脂质A片段可能对脂质A片段诱导的B淋巴细胞酪氨酸磷酸化有重要作用。使用酪氨酸激酶抑制剂herbimycin A和Lenistein治疗可以消除lps诱导的酪氨酸磷酸化和增殖反应，这表明lps诱导的酪氨酸磷酸化可能是一个重要的信号事件，可能导致细胞反应。然而，用磷酸酶抑制剂（苯larsin oxide）治疗没有明显的效果。此外，B淋巴细胞中丝氨酸苏氨酸蛋白磷酸化的增加也可能是重要的，因为LPS刺激后的增殖反应被丝氨酸苏氨酸激酶抑制剂staurosponne预孵育抑制。综上所述，目前的研究结果表明，口腔病变细菌具有通过脂质a片段诱导B淋巴细胞刺激的强大特性，其中酪氨酸磷酸化的增加以及随后的其他蛋白质磷酸化可能是可能导致细胞反应的重要信号事件。少

In this study using the Iipopolysaccharides (LPS) from Porphyronwnas gingivalis as well as other periodontopathic bacteria including Prevotella intermedia, Actinobacillus actinomycetemcomitans and Eikenella corrodens (PgLPS, AaLPS, PiLPS and EiLPS, respectively), the nature of LPS-induced signal transduction mechanism that mediates later cellular responses of Blymphocytes was examined. When detected under Western blot analysis by using the monoclonal anti-phosphotyrosine antibody, all the LPSs as well as Escherichia coli LPS (EcLPS) induced tyrosine phosphorylation in the B lymphocytes from LPS-responsive C3H/HeN mice. In the LPS-hyporesponsive C3H/HeJ B lymphocytes, however, the trigger signals could be induced by PgLPS and PiLPS, but not by AaLPS or EiLPS.Furtherrnore, lipid A from Salmonella minnesota also induced tyrosine phosphorylation in C3H/HeN B lymphocytes. It was reported that the lipid A moieties of PgLPS and PiLPS were quite different from those of EcLPS, AaLPS or EiLPS.Th … More us, these results si.iggest that lipid A moiety of LPS could be potent for the LPS-induced tyrosine phosphoxylation in B lymphocytes. The treatment with tyrosine kinase inhibitors, herbimycin A and Lenistein, abrogated the LPS-induced tyrosine phosphorylation and the proliferative response, suggesting that LPS-induced tyrosine phosphorylation could be an important signaling event that might lead to cellular responses. However, no obvious effect has been observed by the treatment with a phosphatase inhibitor (phenylarsine oxide). In addition, increased serine threonine protein phosphorylation in B lymphocytes could be also important, since the proliferative response following LPS stimulation was inhibited by the preincubation with a serine threonine kinase inhibitor, staurosponne. Taken together, the present findings suggest that the pen odontopathic bacteria have a potent property to induce the stimulation of B lymphocytes by the lipid A moiety, in which increased tyrosine phosphorylation folJowed by other protein phosphorylations could be important signaling events that might lead to cellular responses. Less